McQuillan Andrew M, Eikelboom John W, Hankey Graeme J, Baker Ross, Thom Jim, Staton Janelle, Yi Qilong, Cole Vanessa
Department of Hematology, Royal Perth Hospital, Box X2213 GPO, Perth, WA 6897, Australia.
Stroke. 2003 Oct;34(10):2415-9. doi: 10.1161/01.STR.0000092124.52084.4B. Epub 2003 Sep 11.
Protein Z is a vitamin K-dependent plasma protein whose significance in arterial thrombosis remains uncertain. The objectives of this study were to determine the association between protein Z, ischemic stroke, and etiologic subtypes of ischemic stroke.
We conducted a case-control study of 173 hospital cases of first-ever ischemic stroke and 186 randomly selected community controls. Using established criteria, we classified cases of stroke by etiologic subtype. Protein Z concentrations were measured during the first 7 days and at 3 to 6 months after the acute stroke event.
Blood levels of protein Z measured within 7 days of acute stroke were significantly higher in cases than in controls (geometric mean, 1.46 versus 1.16 microg/mL; P<0.0001). Compared with the lowest tertile, the upper 2 tertiles of protein Z were associated with an adjusted odds ratio (OR) of ischemic stroke of 1.75 (95% CI, 1.00 to 3.07) for the second tertile and 3.07 (95% CI, 1.73 to 5.45) for the upper tertile. The adjusted odds of ischemic stroke caused by large-artery atherothrombosis was nearly 8-fold greater for those with protein Z concentrations in the upper tertile compared with the lower tertile (OR, 7.91; 95% CI, 3.11 to 20.14). The adjusted odds of ischemic stroke due to small-artery disease (OR, 1.79; 95% CI, 0.83 to 3.87) and cardioembolism (OR, 1.80; 95% CI, 0.58 to 5.64) was also increased among individuals with protein Z concentrations in the upper tertile compared with the lower tertile, but not significantly so. There was no significant difference between mean protein Z concentrations among cases in the convalescent phase (3 months) after stroke and age- and sex-matched controls.
There is a strong, independent relationship between elevated blood levels of protein Z and ischemic stroke during the acute phase, particularly ischemic stroke due to large-artery atherothromboembolism, which is no longer evident during the convalescent phase. These results are consistent with the notion that protein Z is either an important factor in the pathogenesis of ischemic stroke due to large-artery atherothromboembolism or an acute phase reactant. Further studies are required to elucidate whether protein Z has a causative or prognostic role in acute arterial thrombosis.
蛋白Z是一种维生素K依赖的血浆蛋白，其在动脉血栓形成中的意义尚不确定。本研究的目的是确定蛋白Z、缺血性卒中及缺血性卒中病因亚型之间的关联。
我们对173例首次发生缺血性卒中的住院患者和186例随机选取的社区对照进行了病例对照研究。根据既定标准，我们按病因亚型对卒中病例进行分类。在急性卒中事件发生后的前7天以及3至6个月时测量蛋白Z浓度。
急性卒中发生后7天内测量的病例组蛋白Z血水平显著高于对照组（几何均值分别为1.46和1.16μg/mL；P<0.0001）。与最低三分位数相比，蛋白Z的上两个三分位数与缺血性卒中的校正比值比（OR）分别为：第二个三分位数为1.75（95%CI，1.00至3.07），最高三分位数为3.07（95%CI，1.73至5.45）。与最低三分位数相比，最高三分位数蛋白Z浓度的患者发生大动脉粥样硬化血栓形成所致缺血性卒中的校正比值几乎高8倍（OR，7.91；95%CI，3.11至20.14）。与最低三分位数相比，最高三分位数蛋白Z浓度的个体发生小动脉疾病所致缺血性卒中（OR，1.79；95%CI，0.83至3.87）和心源性栓塞所致缺血性卒中（OR，1.80；95%CI，0.58至5.64）的校正比值也有所增加，但无显著差异。卒中后恢复期（3个月）病例组的平均蛋白Z浓度与年龄和性别匹配的对照组之间无显著差异。
急性期蛋白Z血水平升高与缺血性卒中之间存在强烈的独立关系，尤其是大动脉粥样硬化血栓形成所致的缺血性卒中，而在恢复期这种关系不再明显。这些结果与蛋白Z要么是大动脉粥样硬化血栓形成所致缺血性卒中发病机制中的重要因素，要么是急性期反应物的观点一致。需要进一步研究以阐明蛋白Z在急性动脉血栓形成中是否具有病因学或预后作用。
